Modeling conjugate vaccine and natural induced antibody correlates of protection for pneumococcal colonization and acute otitis media infection in young children

We measured anti-pneumococcal serotype 19A vaccine-induced antibodies in 160 children (611 sera) after introduction of 13-valent pneumococcal conjugate vaccine and naturally-induced antibodies in 59 children (185 sera) after colonization and acute otitis media (AOM) episodes caused by strains expressing serotype 19A. Correlate of protection (COP) models were constructed using results from multiple prospectively-collected observations in individual children. Generalized estimating equations followed by logistic-regression was used. The COP derived from vaccine-induced antibody levels for prevention of colonization was 5 μg/mL and for AOM was 2.3 μg/mL. A COP for naturally-induced antibody levels for prevention of colonization or AOM could not be derived because an age gradient was not observed. Combining natural- and vaccine-induced antibody levels did not provide biologically plausible COP estimates. We conclude derivation of a COP for prevention of colonization and AOM using individual multi-point child data for pneumococcal serotype 19A can be estimated when an age-gradient is observed.